In recent years, the world has seen an alarming increase in metabolic diseases including obesity, insulin resistance, diabetes, fatty liver disease, and atherosclerosis. For example, over twenty million children and adults in the U.S., or 8% of the population, suffer from diabetes. Atherosclerosis is a leading cause of coronary heart disease and stroke, killing more than 600,000 Americans annually: more than 25% of all deaths in the U.S.
Dysregulation of tissue lipid composition or metabolism can lead to disruption of systemic insulin action and glucose metabolism in adipose, muscle, and liver tissues. Recent studies have clearly identified adipose tissue as a critical site for whole body metabolic regulation. A growing body of evidence supports the concept that peptides and hormones produced within the adipose tissue constitute an important component of the endocrine effects of this site on systemic carbohydrate and lipid homeostasis. There have been important advances in the identification of these molecules and characterization of their biological functions. As the major storage site for body lipids, adipose tissue has also been studied intensively in regards to its role in metabolic regulation through lipids. Although equally critical as peptide hormones, this area has been more challenging to reduce into molecular entities and pathways.
There are two prevailing views about the role of adipose tissue lipid metabolism in metabolic syndrome. First, storage of lipids in adipose tissue has been suggested to protect other organs, especially those that are not well equipped for such burden, from exposure to excessive lipids and thereby reducing the risk of lipotoxicity. Second, fatty acids derived from adipose tissue, particular under pathological conditions like obesity, could disrupt the function of peripheral tissues, resulting in muscle insulin resistance or increased triglyceride accumulation in liver. In these models, the principle consideration has often been the total amount of fatty acid exposure at different target tissues.
Serum fatty acids represent a very complex entity, however, and are composed of structures with varying chain lengths and degrees of saturation. The concentration and composition of fatty acids vary significantly under different physiological and pathological conditions, and these changes are not uniform between cell types and tissues. Although it is unlikely that the total fatty acid levels, alone, could be sufficiently informative, there has been some progress in addressing how different compositions of fatty acids in tissues or circulation may affect the metabolic output locally or systemically, but this has been experimentally challenging. Another intractable question has been how to address lipid storing and/or disposing in tissues responding to the dietary fatty acid intake, and how to adjust the composition to modulate metabolic outcomes. Hence, there remains a need for better understanding of the regulation of systemic fatty acid metabolism, and development of further diagnosis and treatment of fatty acid metabolism-related illnesses.